Details

Autor(en) / Beteiligte

• Mesman, Simone
• van Hooft, Johannes A
• Smidt, Marten P

Titel

Mest/Peg1 Is Essential for the Development and Maintenance of a SNc Neuronal Subset

Ist Teil von

• Frontiers in molecular neuroscience, 2017-01, Vol.9, p.166-166

Ort / Verlag

Switzerland: Frontiers Research Foundation

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Mesodiencephalic dopaminergic (mdDA) neurons originate at the floor plate and floor plate-basal plate boundary of the midbrain ventricular zone. During development mdDA neurons are specified by a unique set of transcription factors and signaling cascades, to form the different molecular subsets of the mdDA neuronal population. In a time series micro-array study performed previously, mesoderm specific transcript ( ) was found to be one of the most upregulated genes during early mdDA neuronal development. Here, we show that transcript is expressed in the midbrain throughout development and becomes restricted to the substantia nigra (SNc) at late stages. In KO animals mdDA neurons are progressively lost in the adult, mostly affecting the SNc, reflected by a 50% decrease of TH protein and DA release in the striatum and a reduction of climbing behavior. Analysis of KO embryos suggest a subtle opposite phenotype to the KO, hinting toward the possibility that specific loss of mdDA neurons in ablated animals could be due to affected WNT-signaling. Interestingly, the mdDA neuronal region affected by the loss of remains relatively unaffected in mutants, suggesting that both genes are essential for the development and/or maintenance of different mdDA neuronal subsets within the SNc. Overall, the neuroanatomical and phenotypical consequences detected upon the loss of , resemble the loss of SNc neurons and loss of movement control as seen in Parkinson's Disease (PD), suggesting that the mouse model may be used as a model-system for PD.